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Androgen deprivation therapy is initially effective for treating patients with advanced prostate cancer; however, the prostate cancer gradually becomes resistant to androgen deprivation therapy, which is termed castration‐resistant prostate cancer (CRPC). Androgen receptor splice variant 7 (AR‐V7), one of the causes of CRPC, is correlated with resistance to a new‐generation AR antagonist (enzalutamide) and poor prognosis. Heat shock protein 70 (Hsp70) inhibitor is known to decrease the levels of full‐length AR (AR‐FL), but little is known about its effects against CRPC cells expressing AR‐V7. In this study, we investigated the effect of the Hsp70 inhibitors quercetin and VER155008 in the prostate cancer cell line LNCaP95 that expresses AR‐V7, and explored the mechanism by which Hsp70 regulates AR‐FL and AR‐V7 expression. Quercetin and VER155008 decreased cell proliferation, increased the proportion of apoptotic cells, and decreased the protein levels of AR‐FL and AR‐V7. Furthermore, VER155008 decreased AR‐FL and AR‐V7 mRNA levels. Immunoprecipitation with Hsp70 antibody and mass spectrometry identified Y‐box binding protein 1 (YB‐1) as one of the molecules regulating AR‐FL and AR‐V7 at the transcription level through interaction with Hsp70. VER155008 decreased the phosphorylation of YB‐1 and its localization in the nucleus, indicating that the involvement of Hsp70 in AR regulation might be mediated through the activation and nuclear translocation of YB‐1. Collectively, these results suggest that Hsp70 inhibitors have potential anti‐tumor activity against CRPC by decreasing AR‐FL and AR‐V7 expression through YB‐1 suppression.

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Previous psychological studies have shown that musical chords primed by Western musical scale in a tonal and modal schema are perceived in a hierarchy of stability. We investigated such priming effects on auditory magnetic responses to tonic-major and submediant-minor chords preceded by major scales and tonic-minor and submediant-major chords preceded by minor scales. Musically trained subjects participated in the experiment. During MEG recordings, subjects judged perceptual stability of the chords. The tonic chords were judged to be stable, whereas the submediant chords were judged to be unstable. Dipole moments of N1m response originating in the auditory cortex were larger in the left hemisphere for the submediant chords than for the tonic chords preceded by the major but not minor scales. No difference in the N1m or P2m moment was found for the chords presented without preceding scales. These results suggest priming effects of the tonal schema, interacting with contextual modality, on neural activity of the auditory cortex as well as perceptual stability of the chords. It is inferred that modulation of the auditory cortical activity is associated with attention induced by tonal instability and modality shift, which characterize the submediant chords.